Age-related non-traumatic fractures are a major health problem. Historically, only bone mass was considered to predict fracture risk but recent studies show that microdamage may also contribute to bone fragility. The relationship between microdamage and bone fragility is not completely understood. Microdamage formation is a combined function of local strain mode and tissue properties. Linear microcracks form under compressive loading and run from cement line to cement line while diffuse damage forms under tensile loading as submicroscopic cracks in interstitial bone. Preliminary studies show older bone forms damage in compression and display an immediate loss of stiffness in the primary phase of fatigue, followed by a short secondary phase. Age-related non-traumatic fractures may, therefore, result from the differences in the mode and magnitude of microdamage formation. Differences in the mode and magnitude of microdamage formation may also alter bone resorption. Preliminary studies demonstrate bone resorption in vitro is restricted to 'packets' of bone separated by cement lines from the unresorbed bone. Direct mechanical insult to the cement line, observed frequently with linear microcracks, may increase bone resorption and contribute to bone fragility. The goal of this proposal is to understand how damage morphology affects bone quality. Four-point bend fatigue tests will be conducted with in vitro resorption and nanoindentation tests to investigate whether: (H1) Cement lines act as a barrier to bone resorption; (H2) Linear microcracks, and not diffuse damage, are associated with a greater loss of stiffness in the primary phase and a shorter secondary phase of bone fatigue; (H3) Linear microcracks are associated with greater bone resorption area than diffuse damage; and (H4) Younger bone forms more diffuse damage than linear microcracks, undergoes proportional local tissue stiffness loss in tension and compression, and has a longer fatigue life. Older bone forms more linear microcracks than diffuse damage, undergoes greater local stiffness loss in compression than in tension, and has a shorter life. This project will: (a) Identify the role of damage morphology in bone quality; (b) Establish a relationship between local tissue properties and damage morphology; and (c) elucidate a cement line based mechanism to restrain osteoclastic bone resorption. [unreadable] [unreadable]